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Purpose To investigate the clinical characteristics and outcomes of primary immunodeficiency diseases (PID) patients complicated with autoimmune disorders (AD). Methods Patients with PID who had been admitted to Peking Union Medical College Hospital (PUMCH) from April 1999 to July 2021 were all retrospectively reviewed. We further analyzed the clinical characteristics and long-term outcomes of common variable immunodeficiency (CVID) patients complicated with AD (CVID-AD), and further compared them with CVID patients without AD (CVID-nAD). Results A total of 241 PID patients were identified with common variable immunodeficiency (CVID) accounting for the majority (99, 41.1%). AD was observed in 31.1% (n = 75) of all PID patients. Among 99 CVID patients, 25 (25.3%) were complicated with AD (CVID-AD), while 74 (74.7%) without AD (CVID-nAD). The Comparison between these two groups indicated that bronchiectasis, skin infection, splenomegaly and lymphadenectasis were more common in CVID-AD group than in CVID-nAD group (all p

Fecal microbiota transplantation (FMT) is a therapy of transplanting the functional flora from the feces of a healthy donor into the gastrointestinal tract of a patient to reconstruct the normal flora.The application of FMT in western medicine dates from the 1950s.After decades of development,the efficacy of FMT has been proven in a variety of diseases.The record of FMT in traditional Chinese medicine (TCM) dates early from the 3rd century A.D.,and relevant theories have been recorded in many TCM works in the past dynasties.FMT as a therapy that has been written into guidelines has been accepted by some countries and regions such as the United States and the United Kingdom in the treatment of

The aim of this study was to describe the clinical features of vocal cord lesions in patients with representative autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).A total of 31 SLE/RA patients (14 SLE and 17 RA) complicated with vocal cord lesions (SLE/RA-VC group) who had been admitted to Peking Union Medical College Hospital were retrieved from the electronic registration system. Ninety-three age and sex-matched SLE/RA patients (42 SLE and 51 RA) without vocal cord lesions (SLE/RA-nVC group) admitted during the same period were chosen randomly as controls. Medical files were reviewed and clinical data collected for comparisons.Vocal cord paralysis (n = 12, 38.7%) and vocal cord mass (n = 14, 45.2%) were the most common types of vocal cord lesions in this cohort. Unilateral lesions were more common than bilateral lesions (67.8% vs 32.3%) and the two sides were affected equally. Two cases of vocal cord bamboo node lesion were observed in SLE-VC group even as an initial manifestation and SLE-VC group had a slightly higher disease activity index (SLEDAI-2K) than their control counterparts (18.56 ± 8.23 vs 13.63 ± 5.89, p = 0.041). The RA-VC group had less pulmonary interstitial disease (29.4% vs 63%, p = 0.017) and lower CRP levels (p = 0.006) than their controls. As for the treatment, 71% of SLE/RA-VC patients had received glucocorticoids and immunosuppressants and 30% had undergone surgery. 45.2% of SLE/RA-VC patients got improvement at the time of discharge.The association of vocal cord lesions with disease activity can be observed in SLE patients but not in RA patients. Vocal cord lesions in SLE/RA patients should be considered as a part of the systemic involvement and should be treated accordingly. Key Points • Vocal cord paralysis and vocal cord mass were the main types of vocal cord lesions in patients with SLE/RA. • Vocal cord lesions in SLE patients may associate with disease activity and vocal cord bamboo node lesions could be an initial manifestation. • Glucocorticoid and immunosuppressants could be effective for vocal cord lesions in SLE/RA patients.

Mediated by Watson-Crick base-pairing principle, DNA can be used to construct multi-functional molecular machines, such as DNA walkers, tweezers, logic gates and motors. It is noteworthy that DNA walkers with the advantages of programmability and diverse structures within the micro-nano scale have attracted intense attention in the field of biosensing, bioimaging, drug delivery, and genetic diagnosis. DNA walkers are comprised of driving power, walking strands and the tracks. The driving power acts as an external stimulus and the tracks as a platform for the walking strands to move autonomously. Under the specific external stimulus as driving power, such as strand displacement strategies, enzymatic reactions and environmental condition stimulus, DNA walkers could realize the generation and amplification of signals. Electrochemiluminescence (ECL) biosensors, combining ECL technology and bio-identification strategies, exhibit the virtue of high sensitivity, wide linear response range and low background interference. Recently, the construction of DNA walker-based ECL biosensors can amplify the targets and signals via multiple identification and recycles, achieving ultrasensitive detection for diverse targets. Herein, this review systematically summarizes the construction of different types of DNA walkers and their applications in ECL biosensors. Ultimately, this review summarizes and discusses the prospects for DNA walkers.

BackgroundSevere autoimmune haemolytic anaemia (AIHA) in systemic lupus erythematosus (SLE) patients could be life-threatening and formidable, especially in those nonresponsive to glucocorticoids (GCs) and immunosuppressants (ISAs). Whole-blood exchange transfusion (WBE), with plasma exchange and pathogenic cell removal as well as healthy red blood cell transfusion, could be beneficial. The objective of this study was to investigate the efficacy and safety of WBE in combination with GCs/ISAs.MethodsIn this retrospective study, the clinical data of 22 refractory severe SLE-AIHA inpatients between February 2016 and February 2021 were collected and analysed, among whom 14 patients had received WBE and were compared with those treated with typical second-line therapy of intravenous immunoglobulin and/or rituximab (IVIG/RTX).ResultsAmong the 22 severe refractory SLE-AIHA patients, eight patients received IVIG and/or RTX without WBE (group 1, IVIG/RTX, n = 8), seven patients were given WBE without IVIG/RTX (group 2, WBE alone, n = 7), and seven patients who failed initial IVIG/RTX therapy were given sequential WBE therapy (group 3 IVIG/RTX→WBE, n = 7). Fourteen patients had accepted WBE treatment regardless of prior IVIG/RTX usage (group 2 + 3, WBE ± IVIG/RTX, n = 14). On days 1, 3, 5, and 7 after corresponding therapies, patients of groups 2, 3, and 2 + 3 showed significantly higher levels of haemoglobin (Hb) than patients of group 1. Compared with patients of group 1, patients of groups 2, 3, and 2 + 3 took less time to reach and maintain Hb ≥60 g/L from baseline. Groups 2 and 2 + 3 consumed a lower dose of GCs than group 1 to reach and maintain Hb ≥60 g/L from baseline. Group 1 experienced longer hospital stays than group 2, and group 3’s cost of hospitalisation is more than groups 1 and 2. Hbmin ConclusionsWBE could be a safe and beneficial alternative therapy for refractory severe SLE-AIHA.

The aim of this study is to investigate the clinical features and outcome of interstitial lung disease (ILD)-onset rheumatoid arthritis (RA) and anti-citrullinated protein antibody (ACPA)-positive ILD-only patients. Arthritis-onset and ILD-onset RA-ILD and ACPA-positive ILD-only patients consecutively admitted to Peking Union Medical College Hospital from January 2008 to December 2017 were enrolled and followed-up. Their demographic, clinical, and laboratory features as well as outcome were collected and analyzed. Compared with arthritis-onset RA-ILD (n = 166, median arthritis-to-ILD interval: 60 months), the ILD-onset RA-ILD (n = 75, median ILD-to-arthritis interval: 2 months) had less rheumatoid nodules and higher titer of ACPA, and manifested more stable ILD (median estimated progression-free survival: 120 vs. 100 months, p = 0.019). Elder age (≥ 65 years) at ILD diagnosis and UIP pattern were associated with ILD progression by both univariate and Cox hazards modeling analysis (p 0.05). In ACPA-positive ILD-only patients (n = 41), arthritis developed in 7 (17.1%) female patients after a median interval of 24 months. ACPA-positive ILD who subsequently developed arthritis exhibited higher frequency of rheumatoid factor (RF), higher titer of ACPA, and higher levels of ESR and CRP (p 0.05). Multivariate regression analysis showed that positive RF (OR 12.55, 95% CI 1.31 to 120.48) was the independent risk factor for arthritis development in ACPA-positive ILD-only patients. ILD-onset RA-ILD had more stable ILD compared with arthritis-onset RA-ILD. ACPA-positive ILD patients with positive RF are at increased risk of developing RA.

The pathogenesis of rheumatoid arthritis (RA), a systemic autoimmune disease characterized by autoreactive T-cell accumulation and pro-inflammatory cytokine overproduction, is unclear. Systematically addressing T-cell receptor (TCR) repertoires of different CD4+ T-cell subsets could help understand RA pathogenesis. Here, peripheral CD4+ T cells from treatment-naïve RA patients and healthy controls were sorted into seven subsets including naïve, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptor β chain repertoires were then analyzed by next-generation sequencing. We identified T-cell clonal expansion in EMT and Th17 cells, with highly similar TCR repertoires between them. Ex vivo experiments demonstrated the preferred differentiation from EMT to Th17 cells in RA. Moreover, TCR diversity in subsets including Th17 was negatively correlated with RA disease activity indices such as C-reactive protein and erythrocyte sedimentation rate. Thus, shared and abnormally expanded EMT and Th17 TCR repertoires might be pivotal for RA pathogenesis.

Acorus macrospadiceus is a common medicinal and food plant used different ethnic groups in Guizhou and surrounding areas. In this paper, the leaf and rhizome tissues of A. macrospadiceus were hydro-distilled to extract the volatile oils. The chemical constituents of these oils were analyzed by GC-MS and identified using the NIST 14.0NIST 14.0s mass spectral libraries. The relative contents of chemical constituents from the different plant parts were determined by area normalization. The analysis of A. macrospadiceus volatile oils resulted in the identification of 25 compounds from the leaf and 36 compounds from the rhizome. The identified compounds accounted for 97.85% of the leaf essential oil content and 97.18% of the rhizome essential oil content. The main volatile constituent of A. macrospadiceus was identified as estragole (93.56% of total oil content in leaf and 71.62% of total oil content in rhizome). Fourteen compounds were found to be common to essential oils of both leaf and rhizome. However, the relative amounts of these compounds were significantly different between the plant parts; the remaining identified compounds were unique to each part. This comparison of volatile oils from the different parts of A. macrospadiceus can serve as a reference for future development. Because of the higher estragole content and better harvesting sustainability of the leaves compared to rhizomes, the leaves of A. macrospadiceus deserve consideration for sustainable development. However, when we use it as a medical plant, we should draw a distinction between it with A. tatarinowii.

The basal thermogenesis of birds is beginning to be viewed as a highly flexible physiological trait influenced by environmental fluctuations, particularly changes in ambient temperature (Ta). Many birds living in regions with seasonal fluctuations in Ta typically respond to cold by increasing their insulation and adjusting their metabolic rate. To understand these metabolic adaptations, body temperature (Tb), metabolic rate (MR), thermal neutral zone (TNZ) and thermal conductance were measured within a range of temperatures from 5 to 40°C in free-living Hwamei, Garrulax canorus, in both winter and summer. Body mass was 61.2±0.3g in winter and 55.5±1.0g in summer, and mean Tb was 41.6±0.1°C in winter and 42.3±0.1°C in summer. TNZ was between 28.3 and 35.1°C in winter and between 28.7 and 33.2°C in summer. The mean basal metabolic rate (BMR) within TNZ was 203.32±11.81ml O2 h(-1) in winter and 168.99±6.45ml O2 h(-1) in summer. Minimum thermal conductance was 3.73±0.09joulesg(-1)h(-1)°C(-1) in winter and 3.26±0.06joulesg(-1)h(-1)°C(-1) in summer. Birds caught in winter had higher body mass, MR, and more variable TNZ than those in summer. The increased winter BMR indicates improved ability to cope with cold and maintenance of a high Tb. These results show that the Hwamei's metabolism is not constant, but exhibits pronounced seasonal phenotypic flexibility associated with maintenance of a high Tb.

Basal metabolic rate (BMR) is thought to be a major hub in the network of physiological mechanisms connecting life history traits. Evaporative water loss (EWL) is a physiological indicator that is widely used to measure water relations in inter- or intraspecific studies of birds in different environments. In this study, we examined the physiological responses of summer-acclimatized Hwamei Garrulax canorus to temperature by measuring their body temperature ( T b ), metabolic rate (MR) and EWL at ambient temperatures ( T a ) between 5 and 40 °C. Overall, we found that mean body temperature was 42.4 °C and average minimum thermal conductance ( C ) was 0.15 ml O 2 g −1 h −1 °C −1 measured between 5 and 20 °C. The thermal neutral zone (TNZ) was 31.8–35.3 °C and BMR was 181.83 ml O 2 h −1 . Below the lower critical temperature, MR increased linearly with decreasing T a according to the relationship: MR (ml O 2 h −1 )=266.59–2.66 T a . At T a s above the upper critical temperature, MR increased with T a according to the relationship: MR (ml O 2 h −1 )=−271.26+12.85 T a . EWL increased with T a according to the relationship: EWL (mg H 2 O h −1 )=−19.16+12.64 T a and exceeded metabolic water production at T a >14.0 °C. The high T b and thermal conductance, low BMR, narrow TNZ, and high evaporative water production/metabolic water production (EWP/MWP) ratio in the Hwamei are consistent with the idea that this species is adapted to warm, mesic climates, where metabolic thermogenesis and water conservation are not strong selective pressures.

MicroRNAs are short endogenous non-coding RNAs that regulate gene expression in various physiological and pathological conditions. To characterize autoantigen-targeting microRNAs in Sjogren’s syndrome (SS), a systematic study was carried out, in which a candidate microRNA set was first identified by bioinformatics analysis and literature search. Then, their gene silencing activities were evaluated with fusion reporter gene and endogenous targets, leading to the identification of three microRNAs: TRIM21-targeting miR-1207-5p, TRIM21-targeting miR-4695-3p, and La autoantigen-targeting miR-299-5p. Compared to healthy controls, downregulation of miR-1207-5p and miR-4695-3p expression was further revealed in the minor salivary glands of primary SS (pSS) patients. This, on the one hand, characterized two autoantigen-targeting microRNAs in Sjogren’s syndrome and, on the other hand, suggested that downregulation of miR-1207-5p and miR-4695-3p expression may lead to increased TRIM21 levels in the minor salivary glands, which contributes to the development of Sjogren’s syndrome.

PTEN regulates normal signaling through the B cell receptor (BCR). In systemic lupus erythematosus (SLE), enhanced BCR signaling contributes to increased B cell activity, but the role of PTEN in human SLE has remained unclear. We performed fluorescence-activated cell sorting analysis in B cells from SLE patients and found that all SLE B cell subsets, except for memory B cells, showed decreased expression of PTEN compared with B cells from healthy controls. Moreover, the level of PTEN expression was inversely correlated with disease activity. We then explored the mechanisms governing PTEN regulation in SLE B cells. Notably, in normal but not SLE B cells, interleukin-21 (IL-21) induced PTEN expression and suppressed Akt phosphorylation induced by anti-immunoglobulin M and CD40L stimulation. However, this deficit was not primarily at the signaling or the transcriptional level, because IL-21-induced STAT3 (signal transducer and activator of transcription 3) phosphorylation was intact and IL-21 up-regulated PTEN mRNA in SLE B cells. Therefore, we examined the expression of candidate microRNAs (miRs) that could regulate PTEN: SLE B cells were found to express increased levels of miR-7, miR-21, and miR-22. These miRs down-regulated the expression of PTEN, and IL-21 stimulation increased the expression of miR-7 and miR-22 in both normal and SLE B cells. Indeed, a miR-7 antagomir corrected PTEN-related abnormalities in SLE B cells in a manner dependent on PTEN. Therefore, defective miR-7 regulation of PTEN contributes to B cell hyperresponsiveness in SLE and could be a new target of therapeutic intervention.

To re-evaluate the diagnoses of ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) and analyze the incidence and reason of misdiagnosis.Patients who were previously diagnosed as AS and nr-axSpA before referrals to Peking Union Medical College Hospital (PUMCH) were re-evaluated by three rheumatologists of PUMCH according to the modified New York criteria for AS and Assessment of SpondyloArthritis international Society (ASAS) axial SpA classification criteria for nr-axSpA.Totally 87 prior AS patients and 53 prior nr-axSpA patients were enrolled in this study. After re-evaluation, 57 patients were still diagnosed as AS and 16 patients were still diagnosed as nr-axSpA. The misdiagnosis incidences were 34.48% and 69.81%, respectively. The misdiagnosis incidence of nr-axSpA was higher than that of AS (P0.01).The misdiagnosis of AS were mainly due to the misjudgment of sacroiliac joints by CT. The misdiagnosis of nr-axSpA were mainly due to the misjudgment of sacroiliac joints by magnetic resonance imaging. Moreover, the misuse of ASAS axial SpA classification criteria contributed to the misdiagnosis also.

To investigate the clinical features of neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) with primary Sjögren's syndrome (pSS).Eleven inpatients diagnosed as NMO secondary to pSS in Peking Union Medical College Hospital were retrospectively analyzed.Eleven patients of pSS with NMO were enrolled in this study, including 10 females and 1 male. The mean age was (35 ± 15) years old. The course of disease ranged from one month to 16 years, with a median of 10 months. The interval between optic nerve and spinal cord involvement was 3 months to 2 years.Eight patients had NMOSD as initial presentations of pSS. Eight patients had history of optic neuropathy. The most frequently involved spinal segment was cervical cord (10 cases) shown by magnetic resonance.Serum NMO-IgG antibodies were tested in 7 patients and 6 of them were positive.NMOSD may present as an important and initial clinical manifestation of pSS, which suggesting the involvement of central nervous system. Autoimmune antibodies, NMO-IgG and imaging were supposed to be done for further evaluation of prognosis and therapy regimens.

p53 is a tumor suppressor and plays a key role in regulating cell hyperplasia, repairing DNA and inducing apoptosis. This study was to investigate p53 expression in fibroblast-like synoviocytes (FLS) and its effect on CD4(+) T lymphocytes from patients with active rheumatoid arthritis (RA).Human FLS were transfected with p53 siRNA and cocultured with CD4(+) T lymphocytes from patients with active RA. The expressions of osteoprotegerin and interleukin (IL)-6 were detected in p53 siRNA and scramble siRNA-transfected FLS. In addition, protein levels of interferon (IFN)-γ, IL-17, IL-4 and CD25 as well as mRNAs of IFN-γ, retinoic acid-related orphan receptor (ROR)-γt, IL-17 and Foxp3 in cocultured CD4(+) T lymphocytes were also measured.IL-6 decreased in p53-knockdown FLS while osteoprotegerin expression was not altered. FLS with p53 deletion significantly increased the production of IL-17 and IFN-γ by CD4(+) T cells and upregulated Foxp3 mRNA expression without effects on the proportion of CD4(+)CD25(high) T lymphocytes.p53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA.

Acclimatization to winter conditions is an essential prerequisite for survival of small passerines of the northern temperate zone. In the present study, we measured diurnal variations in body mass, body temperature and basal metabolic rate (BMR) for seasonally acclimatized Hwameis (Garrulax canorus). Body mass was determined with a Sartorius balance. Metabolic rates of Hwameis were measured with an open-circuit respirometry system. Body masses varied with time of day and were higher in daytime for Hwameis in both summer and winter, and body masses in winter were higher compared to that in summer. Body temperatures of Hwameis were higher in daytime, and the summer acclimatized birds had significantly higher body temperatures compared to the winter acclimatized birds. BMRs of Hwameis were significantly higher during the daytime compared to the nighttime of the daily cycle in both summer and winter, and Hwameis in winter had significantly higher BMRs than that in summer. This result showed that Hwameis rely mostly on metabolic capacity to maintain their body temperature in cold weathers, and Hwameis exhibited daily and seasonal flexibility in morphology and physiology which is important under changing environmental conditions.